An Electrochemistry and Computational Study at an Electrified Liquid-Liquid Interface for Studying Beta-Amyloid...

Area of Science:

• Biophysical Chemistry
• Neuroscience
• Materials Science

Background:

• Amphiphilic peptides like amyloid-beta (Aβ) aggregate and are implicated in neurodegenerative diseases.
• The interface between two immiscible electrolyte solutions (ITIES) serves as a biomimetic system for studying peptide behavior.
• Understanding Aβ aggregation and its modulation by metal ions is crucial for developing therapeutic interventions.

Purpose of the Study:

• To investigate the aggregation and complexation of Aβ(1-42) with Cu(II) ions at an ITIES.
• To evaluate the effect of a peptidomimetic inhibitor (P6) on Aβ(1-42) aggregation.
• To explore the use of electrochemical methods and molecular dynamics simulations for studying these interactions.

Main Methods:

• Utilized cyclic and differential pulse voltammetry (DPV) to monitor Aβ(1-42) complexation and aggregation.
• Employed molecular dynamics simulations to visualize peptide interactions and structural changes at the ITIES.
• Applied Circular Dichroism (CD) spectroscopy to confirm aggregation behavior.

Main Results:

• DPV detected Aβ(1-42) complexation and aggregation with Cu(II) ions, revealing changes in lipophilicity.
• Copper ions induced Aβ(1-42) aggregation, with stoichiometry and binding properties determined by DPV standard addition.
• Molecular dynamics simulations showed Aβ(1-42) forming β-sheet structures, with copper ions promoting strong inter-peptide binding via histidine residues.

Conclusions:

• The ITIES system effectively models Aβ aggregation and metal ion interactions.
• Copper(II) ions significantly influence Aβ(1-42) aggregation pathways by stabilizing β-sheet structures.
• This research provides a foundation for developing inhibitors targeting metal-mediated peptide aggregation.